Glucocorticoid is now widely used as one of the most efficacious medicines against various inflammatory diseases and allergic diseases inclusive of chronic articular rheumatism, lupus erythematosus, and bronchial asthma. The mechanism of its action is attributable to the anti-inflammatory action, anti-edematous action, and immunosuppresive action of glucocorticoid. Of these actions, the mode of anti-inflammatory action relates to the inhibition of the release of arachidonic acid, which is the precursor of prostaglandins or leukotriens regarded to be inflammatory mediators. A new theory has recently been put forward by Flower (Nature 278: 456 (1979)) to the effect that glucocorticoid suppresses the activity of PLA.sub.2 which is a key enzyme to release arachidonic acid directly from the phospholipid. With regard to the mode of action taken by glucocorticoid, it is understood that, upon entering into a cell, glucocorticoid is first bound to the receptor of the cell, and the resulting complex is translocated into the nucleus to activate the specific gene, finally inducing the synthesis of specific protein. Actually, Tsurufuji et al. have shown (in Nature 280: 408 (1979)) that cycloheximide, inhibitor of protein synthesis, and actinomycin D, inhibitor of m RNA synthesis, suppress the therapeutic effect of glucocorticoid against paw edema (experimental animal model of inflammation) caused by serotonin. It is, therefore, sugestive from the abovementioned results that glucocorticoid displays its anti-inflammatory activity through the induction of the synthesis of PLA.sub.2 inhibitory protein.
Attempts have hitherto been made by several groups to isolate such a protein whose synthesis is induced by glucocorticoid and that inhibits the activity of PLA.sub.2 in vitro and suppresses the production of prostaglandin in vivo; however, none of these trials have succeeded in purifying a protein, deducing even a part of its primary structure by protein microsequence analysis, clarifying the composition of amino acid, and, above all, isolating a protein which definitely displays the PLA.sub.2 inhibitory activity.